ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration.

ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Research Abstract Details 

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ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Abstract Text:

Rhona Seijffers,Charles D Mills,Clifford J Woolf,

Peripheral axons of dorsal root ganglion (DRG) neurons, but not their central axons in the dorsal columns, regenerate after injury. However, if the neurons are conditioned by a peripheral nerve injury into an actively growing state, the rate of peripheral axonal growth is accelerated and the injured central axons begin to regenerate. The growth-promoting effects of conditioning injuries have two components, increased axonal growth and a reduced response to inhibitory myelin cues. We have examined which transcription factors activated by peripheral axonal injury may mediate the conditioning effect by regulating expression of effectors that increase the intrinsic growth state of the neurons. Activating transcription factor 3 (ATF3) is a prime candidate because it is induced in all injured DRG neurons after peripheral, but not central, axonal damage. To investigate if ATF3 promotes regeneration, we generated transgenic mice that constitutively express this transcription factor in non-injured adult DRG neurons. The rate of peripheral nerve regeneration was enhanced in the transgenic mice to an extent comparable to that produced by a preconditioning nerve injury. The expression of some growth-associated genes, such as SPRR1A, but not others like GAP-43, was increased in the non-injured neurons. ATF3 increased DRG neurite elongation when cultured on permissive substrates but did not overcome the inhibitory effects of myelin or promote central axonal regeneration in the spinal cord in vivo. We conclude that ATF3 contributes to nerve regeneration by increasing the intrinsic growth state of injured neurons.

ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Publishing Authors By Initials

R Seijffers,CD Mills,CJ Woolf,

For similar nervous system: peripheral nervous system: peripheral nerves research abstracts see: nervous system: peripheral nervous system: peripheral nerves research

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ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of neuroscience : the official journal

VOLUME: 27

Page Numbers: 7911-20

Journal Abbreviation: J. Neurosci.

ISSN: 1529-2401

DAY: 25

MONTH: Jul

YEAR: 2007

ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8102140

ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Keywords Mesh Terms:

KEYWORDS: Peripheral Nerves

MESH TERMS: metabolism

Chemical & Substance for Abstract: ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. Information

Substance Name: Activating Transcription Factor 3

Registry Number: 0

Grant and Affiliation Information for ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration.

AFFILIATION: Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS45459

ACRONYM: NS

MEDLINETA: J Neurosci

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